The overall aim of this project is to test the hypotheses in humans that 1. Cardiac hypertrophy is accompanied by a change in myosin isozymic composition for normal to one with a lower myosin ATPase activity and 2. That this isozymic change is accompanied by a change in haemodynamic performance. These hypotheses will be tested by evaluating the haemodynamic capacity of the left ventricle using sensitive catheterization techniques and measuring biochemical parameters of a biopsy from the same heart taken at surgery which will be subjected to some or all of the following biochemical studies: 1) Actin2+ activated cardiac myosin ATPase studies. This will also include an investigation of Ca sensitivity in a fully regulated (troponintropomyosin) system. 2) Correlation of ATPase activity with isozyme and subunit patterns of myosin. In this respect it will be important to determine whether or not the relationship between ATPase activity and the distribution of myosin isozymes remains the same as in normal hearts. 3) Exploration of possible abnormalities in Ca2+ uptake by sarcoplasmic reticulum. 4) Partial proteolysis of myosin to identify and relate fragments from hypertrophy to fragments obtained from normal isozymic forms of cardiac myosin. The proposed work is thus designed to establish the molecular basis for physiologic and pathologic changes which may occur as a result of cardiac hypertrophy in humans, on the basis of highly sensitive biochemical "fingerprints." Such as single and 2 dimensional gel electrophoresis on native proteins and peptides we will be able to distinguish whether the isozyme changes are i). a shift in the ratio of normally appearing proteins or ii). new molecular species, not found in hearts without hypertrophy. We will establish the functional significance of these biochemical changes by correlating them with haemodynamic data on each heart.